Swiss show that concerns about potency of HIV therapy in context of non-subtype B infections are unfounded

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Patients infected with non-B HIV subtypes have virological outcomes which are at least as good – if not better – than those seen in patients with subtype B infection, Swiss investigators report in the online edition of Clinical Infectious Diseases.

Some research has suggested that patients with non-B subtypes fare less well on HIV therapy. However, there was concern that such studies did not take into account host factors, such as race and cultural issues. It is therefore important that white Swiss patients infected with non-B HIV subtypes were eligible for inclusion in the Swiss study.

“In the past decade, a debate has arisen as to whether antiretroviral compounds are less active against non-B infections, because most antiretroviral drugs were designed to be used against subtype B infections,” write the authors. “Our findings indicate that these concerns are unwarranted.”

Glossary

subtype

In HIV, different strains which can be grouped according to their genes. HIV-1 is classified into three ‘groups,’ M, N, and O. Most HIV-1 is in group M which is further divided into subtypes, A, B, C and D etc. Subtype B is most common in Europe and North America, whilst A, C and D are most important worldwide.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

natural history

The natural development of a disease or condition over time, in the absence of treatment.

sensitivity analysis

An additional analysis of data, also known as a “what–if” analysis, which indicates how robust the study’s results are. Specific assumptions or variables may be changed, to estimate the outcome in a range of scenarios.

treatment interruption

Taking a planned break from HIV treatment, sometimes known as a ‘drugs holiday’. As this has been shown to lead to worse outcomes, treatment interruptions are not recommended. 

There are several distinct HIV subtypes as well as several recombinant forms of the virus. Subtype B predominates in Europe and North America and clinical trials leading to the approval of most antiretroviral drugs involved patients with subtype B.

Only 10% of global HIV infections are caused by subtype B. Studies performed in areas where non-subtype B infections predominate have yielded promising results about the effectiveness of antiretroviral therapy. However, these results cannot be generalised to western countries.

Therefore, investigators from the Swiss HIV Cohort Study examined the virological response to HIV therapy among white patients, comparing outcomes in individuals with subtype B and non-subtype B infections.

“HIV subtype and ethnicity are strongly correlated and ethnicity is potentially associated with treatment response and a different natural history of HIV,” comment the investigators. “This study allows the exclusion of potential bias due to different host genetic backgrounds.”

Data obtained between 1996 and early 2011 were included in the investigators’ analysis.

A total of 4729 patients (90%) had subtype B infection and 539 individuals (10%) were infected with non-subtype B virus. The most common non-B subtypes were AG (24%), A (23%), C (18%) and AE (13%). Baseline CD4 cell count and viral load were broadly comparable between the patients with subtype B and non-subtype B infections.

The incidence of virological failure (a rebound in viral load to above 1000 copies/ml after previous suppression below 400 copies/ml) was higher in patients with subtype B than among those with non-subtype B infections. Overall, the incidence was 4.3 failures per 100 person years for individuals with subtype B infections compared to 1.8 failures per 100 person years for those with non-subtype B infections.

Patients with non-subtype B infections were similarly less likely to experience virological failure when analysis was restricted to treatment-naïve individuals who started therapy after 1999, with failure defined as rebound in viral load from below 50 copies/ml to above 500 copies/ml (1.4 per 100 person years vs. 2.6 per 100 person years).

An especially low risk of virological failure was associated with subtype CRF02_AG  (HR = 0.54; 95% CI, 0.29-0.98) and subtype AG (HR = 0.39; 95% CI, 0.19-0.79).

The association between non-subtype B infections and a reduced risk of virological failure remained robust after controlling for age, sex, HIV transmission category, type of HIV therapy, as well as baseline CD4 cell count and viral load. This was the case for both definitions of virological failure (p = 0.009 and p = 0.041 respectively).

Reported adherence levels were similar for patients with subtype B and non-subtype B infections. Sensitivity analyses that took into account factors such as treatment interruption, mode of transmission, and baseline resistance did not have a significant impact on the investigators’ findings.

“Previous concerns that antiretroviral treatment response might be hampered by development and testing of antiretroviral compounds in resource-rich countries with high subtype B prevalence are no longer tenable, and concerns that non-B infections are less susceptible to cART [combination antiretroviral therapy] are unwarranted,” conclude the investigators. “In fact, patients infected with particular non-B subtypes had lower virological failure rates than patients with subtype B infections in Switzerland.”

This news report is also available in Portuguese.

References

Scherrer AU et al. Improved virological outcome in white patients infected with HIV-1 non-B subtypes compared with subtype B. Clin Infect Dis, doi: 10.1093/cid/cir669, 2011 (click here for the free abstract).